It has been known since the 1940's that .beta.-lactam antibiotics, such as the penicillins and cephalosporins, are effective by reason of their interference with the integrity of bacterial cell walls. It has also been discovered that the interference is effected by covalent bonding to the active site serine residue of one or more of a group of enzymes termed penicillin binding proteins (PBP's). These enzymes serve to complete bacterial cell wall synthesis by a cross linking of peptidoglycan chains, and are essential to the cells. All known PBP's include a sequence -Ser-X-X-Lys- and the simplest kinetic description of the reaction between a PBP and a .beta.-lactam antibiotic is given in equation 1, below, where A is a generalized structure. Since the PBP is regenerated in the deacylation step, useful antibacterial activity is considered to require k.sub.3 /K.gtoreq.1000M.sup.-1 sec.sup.-1 and k.sub.4 .ltoreq.1.times.10.sup.-4 sec.sup.-1. ##STR2##
The question is, therefore, what is the correlation, if any, between antibacterial activity and the "lock and key" interactions which take place between the PBP and the antibiotic.